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| Name | Class |
|---|---|
| University of Massachusetts, Worcester | OTHER |
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This study will investigate the breadth of protection against meningococcal disease in humans immunized with a newly FDA approved meningococcal B vaccine, trade name "TrumenbaĀ®" manufactured by Pfizer Vaccines. As a secondary goal the investigators will investigate underlying mechanisms by which human anti-FHbp antibodies elicit complement-mediated bactericidal activity.
Neisseria meningitidis causes meningitis and severe infections of the blood stream. The incidence of serogroup B meningococcal disease however is too low to conduct a randomized, controlled trial to determine the actual efficacy of the new serogroup B vaccines. Instead vaccine efficacy was inferred from serum bactericidal antibody responses using four test strains. However, because of strain variability of FHbp amino acid sequence (there are more than 800 sequence variants described) and strain variability of FHbp expression, bactericidal data on only four strains are unlikely to be sufficient to predict the actual strain coverage by the vaccine. There also are gaps in knowledge about the underlying mechanisms by which human antibodies to FHbp elicit complement mediated bactericidal activity. For example, binding of FH to FHbp is specific for human FH. Therefore in vaccinated humans the vaccine antigen is expected to form a complex with FH right after immunization. The investigators' hypothesis is that binding of human FH to the vaccine antigen skews the antibody repertoire to FHbp epitopes located outside of the FH combining site. The resulting antibodies would be expected not to inhibit binding of FH to the bacteria. This hypothesis will be investigated in Trumenba-immunized humans as part of studies in Aim 1 (and in future studies of recombinant human anti-FHbp Fabs that will be enabled by obtaining DNA from individual B cells, described in Aim 2).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Label: MenB-FHbp | Experimental | Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals) | Biological | All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule. |
| Measure | Description | Time Frame |
|---|---|---|
| Breadth of Protective Activity of Serum Anti-FHbp Antibody Responses of Adults Immunized With Trumenba Vaccine as Assessed by Serum Bactericidal Titers | Determine the percentage of subjects achieving serum bactericidal titers of 1:4 or greater in serum obtained 1 month after doses 2 and 3 as measured against a panel of 15 genetically diverse meningococcal strains. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Antibody Repertoire to FHbp | Determine the percentage of recombinant anti-FHbp Fabs isolated from B cells of each subject that react with 3 FHbp amino acid sequence variants representative of FHbp variant groups 1, 2 and 3 | 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dan Granoff, MD | Children's Hospital Oakland Research Institute, Center for Immunobiology and Vaccine Development | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States | ||
| University of Massachusetts Medical School |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28566335 | Result | Lujan E, Partridge E, Giuntini S, Ram S, Granoff DM. Breadth and Duration of Meningococcal Serum Bactericidal Activity in Health Care Workers and Microbiologists Immunized with the MenB-FHbp Vaccine. Clin Vaccine Immunol. 2017 Aug 4;24(8):e00121-17. doi: 10.1128/CVI.00121-17. Print 2017 Aug. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Label: MenB-FHbp | Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals) Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals): All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The data from one subject enrolled in the study were excluded due to a diagnosis of cancer after dose 2.
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| ID | Title | Description |
|---|---|---|
| BG000 | Open Label: MenB-FHbp | Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals) Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals): All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Breadth of Protective Activity of Serum Anti-FHbp Antibody Responses of Adults Immunized With Trumenba Vaccine as Assessed by Serum Bactericidal Titers | Determine the percentage of subjects achieving serum bactericidal titers of 1:4 or greater in serum obtained 1 month after doses 2 and 3 as measured against a panel of 15 genetically diverse meningococcal strains. | Posted | Number | percentage of participants | 18 months |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open Label: MenB-FHbp | Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals) Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals): All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| rash | Skin and subcutaneous tissue disorders | Systematic Assessment | One subject developed a severe local reactions after doses 1 and 2. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dan Granoff, MD (Principal Investigator) | Children's Hospital Oakland Research Institute (CHORI) | 510-428-3000 | 7640 | dgranoff@chori.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 14, 2019 | Sep 25, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008589 | Meningococcal Infections |
| ID | Term |
|---|---|
| D016870 | Neisseriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| C000729870 | MenB-FHbp vaccine |
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|
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| Worcester |
| Massachusetts |
| 01655 |
| United States |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Antibody Repertoire to FHbp | Determine the percentage of recombinant anti-FHbp Fabs isolated from B cells of each subject that react with 3 FHbp amino acid sequence variants representative of FHbp variant groups 1, 2 and 3 | This was an exploratory objective requiring new technology. It was done on 0/17 subjects because of technical limitation. | Posted | 1 year |
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| 0 |
| 18 |
| 0 |
| 18 |
| 1 |
| 18 |
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| D007239 | Infections |